Long-term follow-up after vertebroplasty - A mean 10-years follow-up control study.

Objectives: To evaluate the clinical 10 year outcome of patients treated with percutaneous vertebroplasty for vertebral compression fractures and to determine the incidence of new fractures in this time interval, as well as the mortality of the patients who underwent this procedure. Methods: All patients undergoing vertebroplasty for vertebral compression fractures between May 2007 until July 2008 were prospectively followed up at 10 years postoperatively. Patients were assessed for radiologic outcome and self-reported outcome parameters (PROs). Gathered parameters remained unmodified to the initial ones analyzing QoL improvement (EQ5D 3L and NASS score) and pain alleviation (VAS, NRS). Mortality was defined as an additional endpoint. Exclusion criteria include additional instrumentation, use of additional devices such as kyphoplasty balloons/stentoplasty, cognitive impairment, insufficient radiological documentation or absent re-consent. Results: Of 280 patients who underwent vertebroplasty, 49 (17.5%) were available for re-assessment with a mean follow-up of 10.5 years (9.9-11.1). Thirty patients (10.7%) were assessed clinically and radiologically, 16 (5.7%) in written form and three (1.1%) by phone only. A total of 186 (66.4%) died during the follow up period. Out of the remaining 45 patients, 27 patients declined participation, eight couldn't participate due to cognitive impairment, four had insufficient radiologic documentation. Six patients were lost to follow-up. At 10 years, patients reported a consistently improved quality of life (EQ-5D; p < 0.01) and global satisfaction. Vertebroplasty demonstrated a substantial and enduring effect on alleviating back pain over 10 years (p < 0.001). 26 (53%) patients experienced a new fracture since the initial procedure. Conclusion: A decade following vertebroplasty, patients continue to demonstrate a quality of life and pain level comparable to short and medium-term assessments, with a significant difference from baseline measurements. More than half (53%) of the patients participating at last follow-up experienced new fractures during this interim period. The cohort as a whole has been impacted by an elevated mortality rate over the time period.

Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells.

PURPOSE: This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. METHODS: hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1ß. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 µM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model. RESULTS: IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1ß treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation. CONCLUSION: Cxb can inhibit PGE-2 production in hAFCs in an IL-1ß-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.

Anterior thoracolumbar column reconstruction with the vertebral body stent-safety and efficacy.

PURPOSE: The aim of this study was to assess safety and efficacy of vertebral body stenting (VBS) by analyzing (1) radiographic outcome, (2) clinical outcome, and (3) perioperative complications in patients with vertebral compression fractures treated with VBS at minimum 6-month follow-up. METHODS: In this retrospective cohort study, 78 patients (61 ± 14 [21-90] years; 67% female) who have received a vertebral body stent due to a traumatic, osteoporotic or metastatic thoracolumbar compression fracture at our hospital between 2012 and 2020 were included. Median follow-up was 0.9 years with a minimum follow-up of 6 months. Radiographic and clinical outcome was analyzed directly, 6 weeks, 12 weeks, 6 months postoperatively, and at last follow-up. RESULTS: Anterior vertebral body height of all patients improved significantly by mean 6.2 ± 4.8 mm directly postoperatively (p < 0.0001) and remained at 4.3 ± 5.1 mm at last follow-up compared to preoperatively (p < 0.0001). The fracture kyphosis angle of all patients improved significantly by mean 5.8 ± 6.9 degrees directly postoperatively (p < 0.0001) and remained at mean 4.9 ± 6.9 degrees at last follow-up compared to preoperatively (p < 0.0001). The segmental kyphosis angle of all patients improved significantly by mean 7.1 ± 7.6 degrees directly postoperatively (p < 0.0001) and remained at mean 2.8 ± 7.8 degrees at last follow-up compared to preoperatively (p = 0.03). Back pain was ameliorated from a preoperative median Numeric Rating Scale value of 6.5 to 3.0 directly postoperatively and further bettered to 1.0 six months postoperatively (p = 0.0001). Revision surgery was required in one patient after 0.4 years. CONCLUSION: Vertebral body stenting is a safe and effective treatment option for osteoporotic, traumatic and metastatic compression fractures.

Radiofrequency Neurotomy Does Not Cause Fatty Degeneration of the Lumbar Paraspinal Musculature in Patients with Chronic Lumbar Pain-A Retrospective 3D-Computer-Assisted MRI Analysis Using iSix Software.

OBJECTIVE: The present study aimed (1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN) and (2) to compare it to the contralateral non-treated side. DESIGN: Retrospective cohort study. SETTING: Inselspital, University Hospital Bern, University of Bern. SUBJECTS: Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3-L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008 and 2017 were included. METHODS: All patients received a magnetic resonance imaging (MRI) of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed three-dimensionally on standard T2-MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side. RESULTS: A total of 31 treated and 9 non-treated sides (Level L2/3-L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 [0.9 - 2.6] years after RFN (P = .726). We found no differences in the relative fat volume between the treated and non-treated side before (P = .481) and after (P = .578) RFN. CONCLUSIONS: Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation.

Asia Now Surpasses Europe in Spine Research Productivity: An Analysis From 1976-2020.

STUDY DESIGN: Bibliometric review. OBJECTIVE: This study aims to understand the worldwide research productivity trends in spine-related research over the past five decades. SUMMARY OF BACKGROUND DATA: Research productivity in the field of spine surgery has increased tremendously over the past decades. However, knowledge regarding the detailed regional disparity is limited. METHODS: We evaluated original research articles published in four prestigious journals on spine research (European Spine Journal, Journal of Neurosurgery: Spine, Spine, and The Spine Journal) from 1976 to 2020. For 1 year of each decade, the origin of the first and the senior author was assigned to their region of origin. For the year 2020, a detailed analysis of countries and states of origin was performed, and the number of articles was normalized by registered MDs per country (per 10,000 population). RESULTS: We included a total of 4436 articles and 8776 authors for analysis. From 1976 to 2020, the percentage of publications originating from North America decreased (77%-38%). In contrast, Asian contributions drastically increased (3%-36%), whereas articles originating from Europe only slightly raised (20%-22%). In 2020, the United States was the most productive country worldwide (34% with most articles from New York (19%), followed by China (16%) and Japan (10%). After normalization to registered MDs (per 10,000 population), the United States proved to have the highest number of articles. Besides this, India now ranked fourth and Egypt eighth in terms of the most productive countries per MDs. CONCLUSION: North America contributed the largest share of all articles published in the last five decades. Asia, which ranks second in 2020, has overtaken Europe. Normalization to registered MDs can be a helpful tool to reflect a country's research productivity more accurately.Level of Evidence: 3.

PMMA-Cement-PLIF Is Safe and Effective as a Single-Stage Posterior Procedure in Treating Pyogenic Erosive Lumbar Spondylodiscitis-A Single-Center Retrospective Study of 73 Cases.

BACKGROUND: Surgical treatment for erosive pyogenic spondylodiscitis of the lumbar spine is challenging as, following debridement of the intervertebral and bony abscess, a large and irregular defect is created. Sufficient defect reconstruction with conventional implants using a posterior approach is often impossible. Therefore, we developed the "Cement-PLIF", a single-stage posterior lumbar procedure, combining posterior lumbar interbody fusion (PLIF) with defect-filling using antibiotic-loaded polymethylmethacrylate (PMMA). This study first describes and evaluates the procedure's efficacy, safety, and infection eradication rate. Radiological implant stability, bone-regeneration, sagittal profile reconstruction, procedure-related complications, and pre-existing comorbidities were further analyzed. METHODS: A retrospective cohort study analyzing 73 consecutive patients with a minimum of a one-year follow-up from 2000-2017. Patient-reported pain levels and improvement in infectious serological parameters evaluated the clinical outcome. Sagittal profile reconstruction, anterior bone-regeneration, and posterior fusion were analyzed in a.p. and lateral radiographs. A Kaplan-Meier analysis was used to determine the impact of pre-existing comorbidities on mortality. Pre-existing comorbidities were quantified using the Charlson-Comorbidity Index (CCI). RESULTS: Mean follow-up was 3.3 (range: 1-16; ±3.2) years. There was no evidence of infection persistence in all patients at the one-year follow-up. One patient underwent revision surgery for early local infection recurrence (1.4%). Five (6.9%) patients required an early secondary intervention at the same level due to minor complications. Radiological follow-up revealed implant stability in 70/73 (95.9%) cases. Successful sagittal reconstruction was demonstrated in all patients (p < 0.001). There was a significant correlation between Kaplan-Meier survival and the number of pre-existing comorbidities (24-months-survival: CCI ≤ 3: 100%; CCI ≥ 3: 84.6%; p = 0.005). CONCLUSIONS: The Cement-PLIF procedure for pyogenic erosive spondylodiscitis is an effective and safe treatment as evaluated by infection elimination, clinical outcome, restoration, and maintenance of stability and sagittal alignment.

The function of CD146 in human annulus fibrosus cells and mechanism of the regulation by TGF-ß.

The mouse outer annulus fibrosus (AF) was previously shown to contain CD146+ AF cells, while in vitro culture and exposure to transforming growth factor-beta (TGF-ß) further increased the expression of CD146. However, neither the specific function of CD146 nor the underlying mechanism of TGF-ß upregulation of CD146+ AF cells have been elucidated yet. In the current study, CD146 expression and its role in cultured human AF cells was investigated studying the cells' capacity for matrix contraction and gene expression of functional AF markers. In addition, TGF-ß pathways were blocked by several pathway inhibitors and short hairpin RNAs (shRNAs) targeting SMAD and non-SMAD pathways to investigate their involvement in TGF-ß-induced CD146 upregulation. Results showed that knockdown of CD146 led to reduction in AF cell-mediated collagen gel contraction, downregulation of versican and smooth muscle protein 22α (SM22α), and upregulation of scleraxis. TGF-ß-induced CD146 upregulation was significantly blocked by inhibition of TGF-ß receptor ALK5, and partially inhibited by shRNA against SMAD2 and SMAD4 and by an Protein Kinase B (AKT) inhibitor. Interestingly, the inhibition of extracellular signal-regulated kinases (ERK) pathway induced CD146 upregulation. In conclusion, CD146 was shown to be crucial to maintain the cell contractility of human AF cells in vitro. Furthermore, TGF-ß upregulated CD146 via ALK5 signaling cascade, partially through SMAD2, SMAD4, and AKT pathway, whereas, ERK was shown to be a potential negative modulator. Our findings suggest that CD146 can potentially be used as a functional marker in AF repair strategies.

Improved estimates of strength and stiffness in pathologic vertebrae with bone metastases using CT-derived bone density compared with radiographic bone lesion quality classification.

OBJECTIVE: The aim of this study was to compare the ability of 1) CT-derived bone lesion quality (classification of vertebral bone metastases [BM]) and 2) computed CT-measured volumetric bone mineral density (vBMD) for evaluating the strength and stiffness of cadaver vertebrae from donors with metastatic spinal disease. METHODS: Forty-five thoracic and lumbar vertebrae were obtained from cadaver spines of 11 donors with breast, esophageal, kidney, lung, or prostate cancer. Each vertebra was imaged using microCT (21.4 µm), vBMD, and bone volume to total volume were computed, and compressive strength and stiffness experimentally measured. The microCT images were reconstructed at 1-mm voxel size to simulate axial and sagittal clinical CT images. Five expert clinicians blindly classified the images according to bone lesion quality (osteolytic, osteoblastic, mixed, or healthy). Fleiss' kappa test was used to test agreement among 5 clinical raters for classifying bone lesion quality. Kruskal-Wallis ANOVA was used to test the difference in vertebral strength and stiffness based on bone lesion quality. Multivariable regression analysis was used to test the independent contribution of bone lesion quality, computed vBMD, age, gender, and race for predicting vertebral strength and stiffness. RESULTS: A low interrater agreement was found for bone lesion quality (κ = 0.19). Although the osteoblastic vertebrae showed significantly higher strength than osteolytic vertebrae (p = 0.0148), the multivariable analysis showed that bone lesion quality explained 19% of the variability in vertebral strength and 13% in vertebral stiffness. The computed vBMD explained 75% of vertebral strength (p < 0.0001) and 48% of stiffness (p < 0.0001) variability. The type of BM affected vBMD-based estimates of vertebral strength, explaining 75% of strength variability in osteoblastic vertebrae (R2 = 0.75, p < 0.0001) but only 41% in vertebrae with mixed bone metastasis (R2 = 0.41, p = 0.0168), and 39% in osteolytic vertebrae (R2 = 0.39, p = 0.0381). For vertebral stiffness, vBMD was only associated with that of osteoblastic vertebrae (R2 = 0.44, p = 0.0024). Age and race inconsistently affected the model's strength and stiffness predictions. CONCLUSIONS: Pathologic vertebral fracture occurs when the metastatic lesion degrades vertebral strength, rendering it unable to carry daily loads. This study demonstrated the limitation of qualitative clinical classification of bone lesion quality for predicting pathologic vertebral strength and stiffness. Computed CT-derived vBMD more reliably estimated vertebral strength and stiffness. Replacing the qualitative clinical classification with computed vBMD estimates may improve the prediction of vertebral fracture risk.

Systematic Review and Meta-Analysis of 3 Treatment Arms for Vertebral Compression Fractures: A Comparison of Improvement in Pain, Adjacent-Level Fractures, and Quality of Life Between Vertebroplasty, Kyphoplasty, and Nonoperative Management.

BACKGROUND: Osteoporotic vertebral fractures (OVFs) have become increasingly common, and previous nonrandomized and randomized controlled trials (RCTs) have compared the effects of cement augmentation versus nonoperative management on the clinical outcome. This meta-analysis focuses on RCTs and the calculated differences between cement augmentation techniques and nonsurgical management in outcome (e.g., pain reduction, adjacent-level fractures, and quality of life [QOL]). METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the following scientific search engines were used: MEDLINE, Embase, Cochrane, Web of Science, and Scopus. The inclusion criteria included RCTs that addressed different treatment strategies for OVF. The primary outcome was pain, which was determined by a visual analog scale (VAS) score; the secondary outcomes were the risk of adjacent-level fractures and QOL (as determined by the EuroQol-5 Dimension [EQ-5D] questionnaire, the Oswestry Disability Index [ODI], the Quality of Life Questionnaire of the European Foundation for Osteoporosis [QUALEFFO], and the Roland-Morris Disability Questionnaire [RDQ]). Patients were assigned to 3 groups according to their treatment: vertebroplasty (VP), kyphoplasty (KP), and nonoperative management (NOM). The short-term (weeks), midterm (months), and long-term (>1 year) effects were compared. A random effects model was used to summarize the treatment effect, including I2 for assessing heterogeneity and the revised Cochrane risk-of-bias 2 (RoB 2) tool for assessment of ROB. Funnel plots were used to assess risk of publication bias. The log of the odds ratio (OR) between treatments is reported. RESULTS: After screening of 1,861 references, 53 underwent full-text analysis and 16 trials (30.2%) were included. Eleven trials (68.8%) compared VP and NOM, 1 (6.3%) compared KP and NOM, and 4 (25.0%) compared KP and VP. Improvement of pain was better by 1.31 points (95% confidence interval [CI], 0.41 to 2.21; p < 0.001) after VP when compared with NOM in short-term follow-up. Pain effects were similar after VP and KP (midterm difference of 0.0 points; 95% CI, -0.25 to 0.25). The risk of adjacent-level fractures was not increased after any treatment (log OR, -0.16; 95% CI, -0.83 to 0.5; NOM vs. VP or KP). QOL did not differ significantly between the VP or KP and NOM groups except in the short term when measured by the RDQ. CONCLUSIONS: This meta-analysis provides evidence in favor of the surgical treatment of OVFs. Surgery was associated with greater improvement of pain and was unrelated to the development of adjacent-level fractures or QOL. Although improvements in sagittal balance after surgery were poorly documented, surgical treatment may be warranted if pain is a relevant problem. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Disproportionate Vertebral Bodies and Their Impact on Lumbar Disc Herniation.

BACKGROUND: The aim of this study was to determine whether the presence of disproportionate vertebral bodies is a risk factor for disc herniation (DH). METHODS: Sixty-seven consecutive patients (m: 31 f: 36) who underwent lumbar discectomy for symptomatic DH at one level between L3 and S1 were retrospectively included. The last three motion segments (3 × 67 = 201) were assessed on sagittal MRI scans. A disproportionate motion segment was defined as the difference of more than 10% of the antero-posterior diameter of two adjacent endplates. RESULTS: DH was present in 6/67 (9%), 26/67 (38.8%), and 35/67 (52.2%) patients at L3/4, L4/5, and L5/S1, respectively. A total of 14 of 67 patients demonstrated a disproportionate motion segment at the discectomy level (20.9%). A total of 23 of the 201 (11.4%) investigated motion segments met our criteria for a disproportionate motion segment. In our study population, when one of the 201 segments was disproportionate, the positive predictive value (PPV) for DH increased toward the lower segments: the PPV at the L5/S1 level was 83.0%. The odds ratio of disproportion for DH was the highest at the L5/S1 level, with 6.0 ± 0.82 (p = 0.017). CONCLUSIONS: The presence of a disproportionate motion segment in the lower spine may lead to a significant higher risk for DH in patients undergoing discectomy.

"How to measure the outcome in the surgical treatment of vertebral compression fractures? A systematic literature review of highly cited level-I studies".

BACKGROUND: The economic burden of vertebral compression fractures (VCF) caused by osteoporosis was estimated at 37 billion euros in the European Union in 2010. In addition, the incidence is expected to increase by 25% in 2025. The recommendations for the therapy of VCFs (conservative treatment versus cement augmentation procedures) are controversial, what could be partly explained by the lack of standardized outcomes for measuring the success of both treatments. Consensus on outcome parameters may improve the relevance of a study and for further comparisons in meta-analyses. The aim of this study was to analyze outcome measures from frequently cited randomized controlled trials (RCTs) about VCF treatments in order to provide guidance for future studies. MATERIAL AND METHODS: We carried out a systematic search of all implemented databases from 1973 to 2019 using the Web of Science database. The terms "spine" and "random" were used for the search. We included: Level I RCTs, conservative treatment or cement augmentation of osteoporotic vertebral fractures, cited ≥50 times. The outcome parameters of each study were extracted and sorted according to the frequency of use. RESULTS: Nine studies met the inclusion criteria. In total, 23 different outcome parameters were used in the nine analyzed studies. Overall, the five most frequently used outcome parameters (≥ 4 times used) were the visual analogue scale (VAS) for pain (n = 9), European Quality of Life-5 Dimensions (EQ-5D; n = 4) and Roland-Morris Disability Questionnaire (RMDQ, n = 4). CONCLUSION: With our study, we demonstrated that a large inconsistency exists between outcome measures in highly cited Level I studies of VCF treatment. Pain (VAS), followed by HrQoL (EQ-5D) and disability and function (RMDQ), opioid use, and radiological outcome (kyphotic angle, VBH, and new VCFs) were the most commonly used outcome parameters.

3D analysis of fatty infiltration of the paravertebral lumbar muscles using T2 images-a new approach.

PURPOSE: Factors influencing paraspinal muscle degeneration are still not well understood. Fatty infiltration is known to be one main feature of the degeneration cascade. The aim of this cross-sectional study was to illustrate the 3D cluster of paraspinal lumbar muscle degeneration on T2-weighted MRI images using our newly developed software application 'iSix'. METHODS: Mono- (Mm. rotatores), multi- (Mm. multifidus) and pluri-segmental (M. erector spinae) lumbar muscles groups were segmented on T2-weighted MR sequences using a novel computer-assisted technique for quantitative muscle/fat discrimination. The degree of fatty infiltration of the three predefined muscle groups was compared on a 3-dimensional basis, with regard to segment involvement and age. General linear models were utilized for statistical comparison. RESULTS: N = 120 segments (age: 52.7; range 16-87 years) could be included. The overall relative fatty infiltration of the mono-segmental muscles was higher (21.1 14.5%) compared to the multi-segmental (16.0 8.8% p = 0.049) and pluri-segmental muscles (8.5 8.0%; p = 0.03). Mono-segmental muscles on the levels L4/5 (22.9 ± 10.2 [CI 17.6-28.2] %) and L5/S1 (27.01 ± 15.1 [CI 21.4-32.7] %) showed a significant higher amount of fat compared to the levels L2/3 (8.2 ± 6.8 [CI 2.2-14.2] %; L4/5 vs. L2/3, p = 0.03; L5/S1 vs. L2/3, p = 0.02) and L3/4 (13.2 ± 5.4 [CI 8.6-17.7]%; L4/5 vs. L3/4, p = 0.02; L5/S1 vs. L3/4, p < 0.01). Multivariate linear regression analyses revealed age and Pfirrmann grade as independent factors for fatty muscle degeneration. CONCLUSIONS: 3D analysis of fatty infiltration is an innovative tool to study lumbar muscle degeneration. Mono-segmental muscles are more severely affected by degeneration compared to multi-/pluri-segmental muscles, especially at the L4/5 and L5/S1 level. Age and disc degeneration independently correlate with muscle degeneration.

Anterior-posterior view by full-body digital X-ray to rule out severe spinal injuries in Polytraumatized patients.

BACKGROUND: Spinal injuries are present in 16-31% of polytraumatized patients. Rapid identification of spinal injuries requiring immobilization or operative treatment is essential. The Lodox-Statscan (LS) has evolved into a promising time-saving diagnostic tool to diagnose life-threatening injuries with an anterior-posterior (AP)-full-body digital X-ray. METHODS: We aimed to analyze the diagnostic accuracy and the interrater reliability of AP-LS to detect spinal injuries in polytraumatized patients. Therefore, within 3 years, AP-LS of polytraumatized patients (ISS ≥ 16) were retrospectively analyzed by three independent observers. The sensitivity and specificity of correct diagnosis with AP-LS compared to CT scan were calculated. The diagnostic accuracy was evaluated by using the area under the ROC (receiver operating characteristic curve) for sensitivity and specificity. Interrater reliability between the three observers was calculated using Fleiss' Kappa. The sensitivity of AP-LS was further analyzed by the severity of spinal injuries. RESULTS: The study group included 320 patients (48.5 years ±19.5, 89 women). On CT scan, 207 patients presented with a spinal injury (65%, total of 332 injuries). AP-LS had a low sensitivity of 9% (31 of 332, range 0-24%) and high specificity of 99% (range 98-100%). The sensitivity was highest for thoracic spinal injuries (14%). The interrater reliability was slight (κ = 0.02; 95% CI: 0.00, 0.03). Potentially unstable spinal injuries were more likely to be detected than stable injuries (sensitivity 18 and 6%, respectively). CONCLUSION: This study demonstrated high specificity with low sensitivity of AP-LS in detecting spinal injuries compared to CT scan. In polytraumatized patients, AP-LS, implemented in the Advanced Trauma Life Support-algorithm, is a helpful tool to diagnose life-threatening injuries. However, if spinal injuries are suspected, performing a full-body CT scan is necessary for correct diagnosis.

Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells.

Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93 promotes gene transcription via the transcriptional regulator SCY1-like pseudokinase 1 independently of ligation of the extracellular domain. In a drug library screen, we identify the anti-emetic agent metoclopramide as an efficient blocker of CD93 signaling. Metoclopramide treatment reduces murine and human LSCs in vitro and prolongs survival of chronic myeloid leukemia (CML) mice through downregulation of pathways related to stemness and proliferation in LSCs. Overall, these results identify CD93 signaling as an LSC-specific regulator of self-renewal and proliferation and a targetable pathway to eliminate LSCs in CML.

Conventional finite element models estimate the strength of metastatic human vertebrae despite alterations of the bone's tissue and structure.

INTRODUCTION: Pathologic vertebral fractures are a major clinical concern in the management of cancer patients with metastatic spine disease. These fractures are a direct consequence of the effect of bone metastases on the anatomy and structure of the vertebral bone. The goals of this study were twofold. First, we evaluated the effect of lytic, blastic and mixed (both lytic and blastic) metastases on the bone structure, on its material properties, and on the overall vertebral strength. Second, we tested the ability of bone mineral content (BMC) measurements and standard FE methodologies to predict the strength of real metastatic vertebral bodies. METHODS: Fifty-seven vertebral bodies from eleven cadaver spines containing lytic, blastic, and mixed metastatic lesions from donors with breast, esophageal, kidney, lung, or prostate cancer were scanned using micro-computed tomography (µCT). Based on radiographic review, twelve vertebrae were selected for nanoindentation testing, while the remaining forty-five vertebrae were used for assessing their compressive strength. The µCT reconstruction was exploited to measure the vertebral BMC and to establish two finite element models. 1) a micro finite element (µFE) model derived at an image resolution of 24.5 µm and 2) homogenized FE (hFE) model derived at a resolution of 0.98 mm. Statistical analyses were conducted to measure the effect of the bone metastases on BV/TV, indentation modulus (Eit), ratio of plastic/total work (WPl/Wtot), and in vitro vertebral strength (Fexp). The predictive value of BMC, µFE stiffness, and hFE strength were evaluated against the in vitro measurements. RESULTS: Blastic vertebral bodies exhibit significantly higher BV/TV compared to the mixed (p = 0.0205) and lytic (p = 0.0216) vertebral bodies. No significant differences were found between lytic and mixed vertebrae (p = 0.7584). Blastic bone tissue exhibited a 5.8% lower median Eit (p< 0.001) and a 3.3% lower median Wpl/Wtot (p<0.001) compared to non-involved bone tissue. No significant differences were measured between lytic and non-involved bone tissues. Fexp ranged from 1.9 to 13.8 kN, was strongly associated with hFE strength (R2=0.78, p< 0.001) and moderately associated with BMC (R2=0.66, p< 0.001) and µFE stiffness (R2=0.66, p< 0.001), independently of the lesion type. DISCUSSION: Our findings show that tumour-induced osteoblastic metastases lead to slightly, but significantly lower bone tissue properties compared to controls, while osteolytic lesions appear to have a negligible impact. These effects may be attributed to the lower mineralization and woven nature of bone forming in blastic lesions whilst the material properties of bone in osteolytic vertebrae appeared little changed. The moderate association between BMC- and FE-based predictions to fracture strength suggest that vertebral strength is affected by the changes of bone mass induced by the metastatic lesions, rather than altered tissue properties. In a broader context, standard hFE approaches generated from CTs at clinical resolution are robust to the lesion type when predicting vertebral strength. These findings open the door for the development of FE-based prediction tools that overcomes the limitations of BMC in accounting for shape and size of the metastatic lesions. Such tools may help clinicians to decide whether a patient needs the prophylactic fixation of an impending fracture.

Finite element models can reproduce the effect of nucleotomy on the multi-axial compliance of human intervertebral discs.

Finite element (FE) models can unravel the link between intervertebral disc (IVD) degeneration and its mechanical behaviour. Nucleotomy may provide the data required for model verification. Three human IVDs were scanned with MRI and tested in multiple loading scenarios, prior and post nucleotomy. The resulting data was used to generate, calibrate, and verify the FE models. Nucleotomy increased the experimental range of motion by 26%, a result reproduced by the FE simulation within a 5% error. This work demonstrates the ability of FE models to reproduce the mechanical compliance of human IVDs prior and post nucleotomy.

Direct anterior decompression of L4 and L5 nerve root in sacral fractures using the pararectus approach: a technical note.

PURPOSE: To describe a new surgical technique for neurolysis and decompression of L4 and L5 nerve root entrapment after vertical sacral fractures via the pararectus approach for acetabular fractures, and to present four case examples. PATIENTS AND METHODS: We retrospectively evaluated four patients suffering radiculopathy from entrapment of the L4 or L5 nerve root in vertical sacral fractures between January and December 2016. The mean follow-up period after surgery was 18 (range 7-27) months. All patients underwent direct decompression and neurolysis of the L4 and L5 nerve roots via the single-incision, intrapelvic, extraperitoneal pararectus approach. RESULTS: In all patients, the L4 and L5 nerve root was successfully visualized and decompressed, proving feasibility of the pararectus approach for this indication. No patient presented with a neural tear. Complete neurologic recovery was present in one patient at last follow-up; two patients had incomplete recovery of their radiculopathy; and one patient had no improvement after nerve root decompression. CONCLUSIONS: The pararectus approach allows for sufficient visualisation and direct decompression and neurolysis of the L4 and L5 nerve root entrapped in vertical sacral fractures. Although neurologic recovery was not achieved in all patients in this small case series, the approach may be a suitable alternative to posterior approaches and other anterior approaches such as the lateral window of the ilioinguinal approach.

Spinopelvic dissociation in patients suffering injuries from airborne sports.

BACKGROUND: Spinopelvic dissociation which is also called U-type or referred to H-type sacral fractures with a transverse fracture line is an infrequent injury that results mainly from high-energy accidents. This results in an osseous dissociation of the upper central segment of the sacrum and the entire spine from the lower sacral segments. The purpose was to investigate the incidence of spinopelvic fracture in general among airborne injuries. PATIENTS AND METHODS: Using our electronic patient records, we retrospectively investigated all sacral fractures related to airborne sports between 2010 and 2017. All injuries were classified according to the Roy-Camille, Denis, AOSpine and the Tile classification system. RESULTS: During the period of interest, 44 patients (18.7%) were admitted with sacral fractures after accidents obtained from airborne sports, including 16 spinopelvic dissociations (36.4%). The majority of these injuries were obtained from paragliding (75.0%), followed by BASE jumping (21.4%) and parachuting (4%). The mean injury severity score (ISS) in the spinopelvic dissociation group was significantly higher compared with other sacral fracture group (38.1 vs. 20.0; p < 0.001). Six lambda-type, four T-type, four H-type and two U-type injuries were identified. In total, four patients (25%) were found to have neurological impairment. For treatment, 87.5% of patients underwent subsequent surgical stabilization. CONCLUSION: Airborne sports have high potential for serious, life-threatening injuries with a high incidence of spinopelvic dissociation. In the literature, the prevalence of spinopelvic dissociation in sacral fractures is described to be between 3 and 5%. In our series, the prevalence is 36.4%. It is important to identify the potential injuries promptly for the further treatment. These slides can be retrieved under Electronic Supplementary Material.

Fibrin-Hyaluronic Acid Hydrogel (RegenoGel) with Fibroblast Growth Factor-18 for In Vitro 3D Culture of Human and Bovine Nucleus Pulposus Cells.

We investigated the effects of a fibrin-hyaluronic acid hydrogel (FBG-HA) and fibroblast growth factor 18 (FGF-18) for nucleus pulposus (NP) regeneration. Healthy bovine (n = 4) and human degenerated NP cells (n = 4) were cultured for 14 days in FBG-HA hydrogel with FGF-18 (∆51-mutant or wild-type) in the culture medium. Gene expression, DNA content, and glycosaminoglycan (GAG) synthesis were evaluated on day 7 and 14. Additionally, histology was performed. Human NP cells cultured in FBG-HA hydrogel showed an increase in collagen type II (COL2) and carbonic anhydrase XII (CA12) gene expression after 14 or 7 days of culture, respectively. GAG release into the conditioned medium increased over 14 days. Healthy bovine NP cells showed increased gene expression of ACAN from day 7 to day 14. Wild type FGF-18 up-regulated CA12 gene expression of human NP cells. Histology revealed an increase of proteoglycan deposition upon FGF-18 stimulation in bovine but not in human NP cells. The FBG-HA hydrogel had a positive modulatory effect on human degenerated NP cells. Under the tested conditions, no significant effect of FGF-18 was observed on cell proliferation or GAG synthesis in human NP cells.